本实验室以往的研究显示，食欲肽（orexin）通过调制视网膜神经元的活动而影响成像视觉。本项目的主题是运用电生理、免疫组化、高效液相色谱及行为学等技术研究orexin如何调制自感光神经节细胞—ipRGC，并进一步影响非成像（NIF）视觉（如昼夜节律、瞳孔对光反射）。包括两部分工作：一是在相应的转基因和基因敲除小鼠上分别研究orexin对视杆、视锥信号通路的调制而影响ipRGC的活动及其机制，二是orexin对ipRGC的内源性光反应（由它所包含的melanopsin介导）的调制及其机制。由于ipRGC投射至NIF视觉核团，orexin对ipRGC活动的调制将影响NIF视觉，这种影响将通过分析条件性敲除orexin基因导致小鼠视网膜或ipRGC中orexin的缺失对NIF视觉的影响加以检测，从而对orexin在NIF视觉中的作用及其机制形成较完整的认识。

Our previous studies showed that orexins affect image-forming vision through modulating activities of retinal neurons. In this project, using electrophysiological recording, immunohistochemistry, high-performance liquid chromatograph (HPLC) and behavior test, we investigate how orexins modulate activities of intrinsically photosensitive retinal ganglion cells (ipRGCs), and further affect non-image-forming (NIF) visual functions, such as circadian rhythm and pupillary light reflex. Firstly, we will investigate modulation by orexins of signals to ipRGCs driven by cone pathway or rod pathway by using transgenic mice, in which functions of rod/cone and ipRGC are genetically deletion. Secondly, we will study how orexins modulate melanopsin-driven (intrinsical) light responses of ipRGCs and its underlying mechanisms. Since ipRGCs project to a variety of brain nuclei mediating NIF visual functions, the orexin effects on ipRGCs will inevitably have impact on NIF vision. Such impact will be analyzed in the conditional orexin gene knockout mice to examine how lacking the orexins selective in the retina or in the ipRGCs affect NIF vision. This study will therefore provide a more complete understanding of the effect of orexins on NIF vision.